Story of Zyvox

The story begins with an international scientific conference held in New York City in 1987. “Dr. Steven Brickner, a synthetic organic chemist, listened to a scientist from Dupont describe an extraordinary new class of antibiotics, called oxazolidinones.” (story) These new compounds were wholly synthetic and simple in their structure, while at the same time possessing excellent pharmacokinetic properties. Also, these compounds inhibited Gram-positive bacteria associated with serious infections, without demonstrating significant cross resistance with any known antibiotics; even in a laboratory, Dupont scientists were unable to induce resistance. Brickner was interested by the results of these antibiotics, and realized how they could be effective against MRSA (a virulent staph infection) and other bugs. Once Brickner arrived back at his home, he began to try and find novel oxazolidinone compounds that might be effective. Within a few months, Brickner and his lab team developed several compounds that mimicked the activity of the Dupont compounds. While they were at this stage, they heard that DuPont had terminated its oxazolidinone research program because their compounds were fairly toxic. Now Brickner’s team had to come up with a compound that was safe. A toxicologist named Dr. Richard Piper offered to run 30-day toxicology studies for the drug. At the end of the thirty days, the results came in and fortunately, the compound was nontoxic. DuPont soon acquired a patent on this lead compound, but the toxicity result bought Brickner more time. But even more importantly, Brickner and his team had “established that a structure toxicity relationship existed for these compounds.” (story) This discovery allowed the team to eventually identify 20-25 subclasses of oxazolidinone, some of which exhibited good antibacterial activity and safety profiles. After this phase of research, the Brickner team began to once again run tox studies. During the many drug trials, the Brickner lab made two important discoveries: “first, in an idoline called U-85112, the introduction of a nitrogen atom on the phenyl group, which gave compounds improved safety; and second, the incorporation of a favored side chain, which would later prove useful in the discovery of Upjohn’s first oxazolidinone candidate, eperzolid.” (from story) The team then focused on one synthesized analog, which lead to the compound known as Zyvox.

This story is interesting to me, because of the huge impact that it made upon the world. With the advent of this drug, many many lives and limbs were saved from destruction by antibiotic-resistant strains of infections. Also, this drug significantly eased the pain and discomfort that the infections inevitably induced. Finally, the fortitude and persistence of the research team makes this drug/story very interesting.

http://www.innovation.org/index.cfm/StoriesofInnovation/InnovatorStories/The_Story_of_Zyvox